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Anguita E.,Hospital Clinico San Carlos IdISSC | Gupta R.,University College London | Olariu V.,Lund University | Valk P.J.,Erasmus University Rotterdam | And 3 more authors.
Developmental Biology | Year: 2016

We identify a mutation (D262N) in the erythroid-affiliated transcriptional repressor GFI1B, in an acute myeloid leukemia (AML) patient with antecedent myelodysplastic syndrome (MDS). The GFI1B-D262N mutant functionally antagonizes the transcriptional activity of wild-type GFI1B. GFI1B-D262N promoted myelomonocytic versus erythroid output from primary human hematopoietic precursors and enhanced cell survival of both normal and MDS derived precursors. Re-analysis of AML transcriptome data identifies a distinct group of patients in whom expression of wild-type GFI1B and SPI1 (PU.1) have an inverse pattern. In delineating this GFI1B-SPI1 relationship we show that (i) SPI1 is a direct target of GFI1B, (ii) expression of GFI1B-D262N produces elevated expression of SPI1, and (iii) SPI1-knockdown restores balanced lineage output from GFI1B-D262N-expressing precursors. These results table the SPI1-GFI1B transcriptional network as an important regulatory axis in AML as well as in the development of erythroid versus myelomonocytic cell fate. © 2016. Source

Worm M.,Charite - Medical University of Berlin | Moneret-Vautrin A.,A+ Network | Scherer K.,University of Basel | Lang R.,Paracelsus Medical University | And 15 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Methods: Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics.Results: Fifty-nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18 years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30 min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first-line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay-or self-treated reactions to food and 27.6% of insect anaphylaxis received on-site adrenaline.Conclusion: This pilot phase of a pan-European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.Background: Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Lecube A.,University of Lleida | Lecube A.,Hospital Universitari Vall dHebron | de Hollanda A.,University of Lleida | Calanas A.,Hospital Universitario Reina Sofia | And 19 more authors.
Obesity Surgery | Year: 2016

Background: Specific data is needed to safely expand bariatric surgery and to preserve good surgical outcomes in response to the non-stop increase in obesity prevalence worldwide. Objective: The aims of this study are to provide an overview of the baseline characteristics, type of surgery, and 30-day postoperative morbidity and mortality in patients undergoing bariatric surgery in Spanish public hospitals, and evaluate changes throughout the 2000–2014 period. Material and Methods: This is a descriptive study using data from the RICIBA, a computerized multicenter and multidisciplinary registry created by the Obesity Group of the Endocrinology and Nutrition Spanish Society. Three periods according to the date of surgery were created: January 2000 to December 2004 (G1), January 2005 to December 2009 (G2), and January 2010 to December 2014 (G3). Results: Data from 3843 patients were available (44.8 ± 10.5 years, a 3:1 female-to-male ratio, 46.9 ± 8.2 kg/m2). Throughout the 15-year period assessed, candidate patients for bariatric surgery were progressively older and less obese, with an increase in associated comorbidities and in the prevalence of men. The global trend also showed a progressive decrease in Roux-en-Y gastric bypass, the most performed bariatric procedure (75.1 % in G1, 69.3 % in G2, and 42.6 % in G3; p < 0.001), associated with a parallel increase in sleeve gastrectomy (0.8 % in G1, 18.1 % in G2, and 39.6 % in G3; p < 0.001). An overall mortality rate of 0.3 % was reported. Conclusions: Data from Spain is similar to data observed worldwide. Information recorded in the National Registries like RICIBA is necessary in order to safely expand bariatric surgery in response to increasing demand. © 2015, Springer Science+Business Media New York. Source

Grabenhenrich L.B.,Charite - Medical University of Berlin | Dolle S.,Charite - Medical University of Berlin | Moneret-Vautrin A.,University of Lorraine | Kohli A.,University of Zurich | And 20 more authors.
Journal of Allergy and Clinical Immunology | Year: 2016

Background: Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description. Objective: We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents. Methods: The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form. Results: Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions. Conclusions: The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition. © 2015 American Academy of Allergy, Asthma & Immunology. Source

Matricardi P.M.,Charite - Medical University of Berlin | Kleine-Tebbe J.,Allergy & Asthma Center Westend | Hoffmann H.J.,Aarhus University Hospital | Valenta R.,Medical University of Vienna | And 67 more authors.
Pediatric Allergy and Immunology | Year: 2016

The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled ‘component-resolved diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Source

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